FDA Accepts Shionogi’s Ensitrelvir NDA for Review as the First Oral Therapy for the Prevention of COVID-19 Following Exposure

Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter “Shionogi”) announced the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) from Shionogi Inc., a New Jersey-based subsidiary of Shionogi, for ensitrelvir (Generic name: ensitrelvir fumaric acid, Code No.: S-217622), an investigational oral antiviral for the prevention of COVID-19 following exposure to an infected individual. The FDA has set an action date of June 16, 2026 under the Prescription Drug User Fee Act (PDUFA).

The NDA is supported by results from the global, double-blind, randomized, placebo-controlled Phase 3 study, SCORPIO-PEP, which studied ensitrelvir as post-exposure prophylaxis (PEP). If approved, ensitrelvir would be the first and only oral therapy for the prevention of COVID-19 following exposure to an infected individual.1,2

SARS-CoV-2 remains highly transmissible and up to half of people living with an infected individual may develop COVID-19.3,4 The virus is constantly evolving, with novel symptoms reported.5,6 COVID-19 continues to impact daily life and may lead to absences from school and work, may cause long COVID, and in some cases, may progress to severe disease.7-12 Even patients with mild COVID-19 may experience worsening of preexisting chronic conditions.13-17

Following exposure to COVID-19, the best way to avoid its potentially serious and long-term complications is to stop viral replication, which prevents the development of the disease.1,2 There are currently no approved antiviral therapies proven to prevent COVID-19 following exposure.1,2,18 COVID-19 vaccines are received before exposure, and they do not stop viral replication.19,20 Other COVID-19 antivirals are taken following exposure and diagnosis, after viral replication has occurred and disease is already established.21

“Shionogi has a long history of innovation in infectious disease treatment and prevention. Our dedication to this field has led to significant breakthroughs in the development of novel antimicrobials and antivirals for HIV/AIDS, influenza and COVID-19. If approved, ensitrelvir will be the first and only oral therapy to help protect people in the U.S. from COVID-19 following exposure," said Nathan McCutcheon, MBA, President and CEO, Shionogi Inc.

About ensitrelvir

Ensitrelvir is a SARS-CoV-2 main protease inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 has an enzyme called the main protease (3-CL), which is essential for the replication of the virus. Ensitrelvir suppresses the replication of SARS-CoV-2 by selectively inhibiting the main protease.

Ensitrelvir, known as Xocova® in countries where it is approved, received emergency regulatory approval in Japan in November 2022 and full approval in March 2024 for the treatment of COVID-19 based on results from SCORPIO-SR, a Phase 3 study conducted in Asia, during the Omicron-dominant phase of the pandemic.

In SCORPIO-SR, ensitrelvir showed both clinical symptomatic efficacy (symptom resolution sustained for at least 24 hours) for five typical Omicron-related symptoms (primary endpoint) and antiviral efficacy (key secondary endpoint) in a predominantly vaccinated population of patients with mild-to-moderate SARS-CoV-2 infection, regardless of risk factors. Most adverse events were mild in severity and no deaths were seen in the study. Among the most common treatment-related adverse events were temporary decreases in high-density lipoprotein and increased blood triglycerides, as observed in previous studies. Results from this study were published in JAMA Network Open.

In 2025, Shionogi submitted two new drug applications in Japan for post-exposure prophylaxis of COVID-19 and for COVID-19 treatment in pediatric patients aged six to under 12 years. The pediatric submission is based on a multicenter, randomized, double-blind, placebo-controlled trial of ensitrelvir in mild-to-moderate COVID-19 patients aged 6 to 12 years in Japan. The study confirmed safety and tolerability and found the pharmacokinetics of ensitrelvir in this age group to be similar to that in adults.

Ensitrelvir became available in Singapore for the treatment of COVID-19 via a Special Access Route application in 2023, and it is currently under regulatory review in Taiwan for the treatment of COVID-19. Ensitrelvir is also under regulatory review with the European Medicines Agency for COVID-19 post-exposure prophylaxis and treatment.22

Ensitrelvir is an investigational drug outside of Japan and Singapore. In addition, the brand name Xocova® has not been approved for use outside of Japan and Singapore and pertains only to the approved drug in Japan and Singapore.

FDA Accepts Shionogi’s Ensitrelvir NDA for Review as the First Oral Therapy for the Prevention of COVID-19 Following Exposure

Achieve Life Sciences Announces FDA Acceptance of Cytisinicline New Drug Application for Treatment of Nicotine Dependence for Smoking Cessation

Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline for treatment of nicotine dependence, today announced that the U.S. Food and Drug Administration (FDA) has accepted the cytisinicline New Drug Application (NDA) for a new treatment for smoking cessation in adults. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) targeted action date of June 20, 2026.

“The FDA’s acceptance of our NDA validates the totality of our product development program,” said Dr. Cindy Jacobs, President and Chief Medical Officer of Achieve Life Sciences. “Our application is supported by a decade of rigorous research and comprehensive data from thousands of participants. We've built compelling scientific and clinical results as a foundation that, if approved, positions cytisinicline to potentially address a significant medical need. We’re eager to engage constructively with the FDA as we progress through the NDA review process.”

The company’s NDA details a comprehensive clinical development program, with more than 2,000 clinical trial participants contributing to the body of evidence. The ORCA-2 and ORCA-3 Phase 3 trials showed cytisinicline administered for either 6 or 12 weeks, alongside standard behavioral support, demonstrated significantly greater smoking abstinence rates by the end of treatment and in long-term abstinence through week 24 as compared to placebo. In addition, safety data will include over 400 participants who have received at least six months of cumulative cytisinicline exposure and over 200 participants receiving at least 1 year of cumulative cytisinicline exposure, with no new safety concerns as reported by the Data Safety Monitoring Committee.

“Smoking is the leading cause of preventable death and disease, claiming the lives of nearly half a million Americans each year, and costing the American economy more than an estimated $600 billion a year,” said Rick Stewart, Chief Executive Officer of Achieve Life Sciences. “The FDA's acceptance of our NDA filing underscores nicotine dependence as an important public health need that demands action. We're energized by this milestone and remain laser-focused on our mission, working toward commercial readiness for the second half of 2026, pending FDA approval. Each year, an estimated 15 million Americans attempt to quit smoking, and we're committed to providing those who are ready to quit a new tool so they can break free from nicotine dependence.”

https://en.wikipedia.org/wiki/Cytisine

Achieve Life Sciences Announces FDA Acceptance of Cytisinicline New Drug Application for Treatment of Nicotine Dependence for Smoking Cessation

Sentynl Therapeutics Updates, Complete Response Letter (CRL) relating to its New Drug Application (NDA) for On Its NDA for CUTX-101

Sentynl Therapeutics, Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, Ltd. (“Zydus”), announced today that the U.S. Food and Drug Administration (USFDA) has issued a Complete Response Letter (CRL) relating to its New Drug Application (NDA) for copper histidinate (CUTX-101), intended to treat Menkes disease in pediatric patients.

The USFDA provided findings within the CRL that Sentynl and Zydus will need to address to clarify the path forward. Specifically, the USFDA mentioned a CGMP inspection of the facility where CUTX-101 is manufactured. Zydus recently provided responses to USFDA’s September 2025 re-inspection demonstrating the facility’s CGMP compliance and is awaiting USFDA’s Establishment Inspection Report (EIR). Sentynl will request a meeting with USFDA to discuss the CRL and resubmission of the CUTX-101 NDA. The CRL did not cite any other approvability concerns, nor did it identify any deficiencies in CUTX-101’s efficacy and safety data.

“We recognize the USFDA’s decision and remain dedicated to working with the Agency to clarify next steps. Our commitment to patients is unchanged. We believe in the promise of our therapy and are prepared to address the feedback and pursue resubmission promptly,” said Matt Heck, CEO, Sentynl.

Menkes disease is a rare X-linked recessive pediatric genetic disease that impacts an estimated 1 in 34,810 to as high as 1 in 8,664 live male births. Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier. CUTX-101 is a subcutaneous injectable formulation of copper histidinate that restores copper homeostasis and maintains copper levels in patients with Menkes disease.

The CUTX-101 NDA was initially granted Priority Review by the FDA and is supported by positive topline clinical efficacy results for CUTX-101, demonstrating significant improvement in overall survival for Menkes disease subjects who received early treatment with CUTX-101.

Sentynl Therapeutics Updates On Its NDA for CUTX-101

FDA Approves Linzess (linaclotide) for Children 7 Years and Older with Irritable Bowel Syndrome with Constipation

The U.S. Food and Drug Administration (FDA) has approved Linzess (linaclotide) capsules for pediatric patients 7 years and older with irritable bowel syndrome with constipation (IBS-C). Linzess is the first treatment approved for IBS-C in pediatric patients.

Disease or Conditions

IBS-C is a common condition affecting children and adolescents characterized by chronic constipation (which occurs when patients have infrequent bowel movements with hard stools that may be difficult or painful to pass), abdominal pain, and bloating. There is no known underlying organic cause and there are typically multiple contributing factors.

Efficacy

The effectiveness of Linzess to treat IBS-C was established in pediatric patients 7 years and older. Linzess for this indication was supported by extrapolation of efficacy from adequate and well-controlled studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients 7 to 17 years who met modified Rome III criteria for child/adolescent IBS-C. The primary endpoint was the proportion of patients who achieved at least a 30% reduction in abdominal pain and an increase of at least two spontaneous (i.e., naturally occurring) bowel movements per week from baseline for at least 6 weeks of the 12-week treatment period. The efficacy results were consistent with results demonstrated in the adult IBS-C population.

Safety

The safety of Linzess in these clinical studies was similar in adult and pediatric patients. The most common side effect reported in pediatric patients 7 to 17 years with IBS-C was diarrhea. If severe diarrhea occurs, patients should discontinue Linzess and be rehydrated. Patients younger than 2 years can be at risk of serious dehydration and should not take Linzess for any indication, nor should patients with known or suspected mechanical gastrointestinal obstruction (bowel blockage). See the full prescribing information for additional information on risks associated with Linzess.

The recommended dosage for pediatric patients 7 years and older with IBS-C is 145 mcg orally once daily.

https://en.wikipedia.org/wiki/Linaclotide

FDA Approves Linzess (linaclotide) for Children 7 Years and Older with Irritable Bowel Syndrome with Constipation

FDA Files Corcept’s New Drug Application for Relacorilant as a Treatment for Patients with Platinum-Resistant Ovarian Cancer

Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today announced that the U.S. Food and Drug Administration (FDA) has accepted Corcept’s New Drug Application (NDA) for relacorilant as a treatment for patients with platinum-resistant ovarian cancer. The FDA has assigned a PDUFA date of July 11, 2026 for the application.

Corcept’s NDA is based on positive data from its pivotal Phase 3 ROSELLA and Phase 2 trials. In these trials, patients who received relacorilant plus nab-paclitaxel experienced improved progression-free and overall survival compared to patients who received nab-paclitaxel monotherapy, with no need for biomarker selection. Relacorilant was well-tolerated, consistent with its known safety profile. Importantly, relacorilant conferred its benefit without increasing the safety burden of the patients who received it. The type, frequency and severity of adverse events in the combination arms were similar to those in the nab-paclitaxel monotherapy arms.

“The FDA's acceptance of our NDA brings us closer to offering a much-needed treatment option to patients with this dire disease,” said Joseph Belanoff, M.D., Corcept’s Chief Executive Officer. “Relacorilant has the potential to redefine how platinum-resistant ovarian cancer is treated.”

About Relacorilant

Relacorilant, an oral therapy, is a selective glucocorticoid receptor (GR) antagonist that modulates cortisol activity by binding to the GR but not to the body's other hormone receptors. Corcept is developing relacorilant in ovarian cancer and a variety of other serious disorders, including endogenous hypercortisolism and prostate cancer. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. It has been designated an orphan drug by the FDA and the European Commission (EC) for the treatment of hypercortisolism and by the EC for the treatment of ovarian cancer. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of December 30, 2025 for relacorilant as a treatment for patients with hypercortisolism.

https://en.wikipedia.org/wiki/Relacorilant

FDA Files Corcept’s New Drug Application for Relacorilant as a Treatment for Patients with Platinum-Resistant Ovarian Cancer

FDA Approves Caplyta (lumateperone) as an Adjunctive Therapy for the Treatment of Major Depressive Disorder (MDD) in Adults

In continuation of my update on lumateperone

Johnson & Johnson (NYSE: JNJ) announced the U.S. Food and Drug Administration (FDA) approval of  Caplyta® (lumateperone) as an adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults. The approval – the first under J&J leadership following its acquisition of Intra-Cellular Therapies, Inc. – provides patients with a safe and effective new treatment option that can enable a path to remission. Caplyta® makes it easy to start and stay on treatment without the need for titration. Weight gain and other metabolic side effects that typically lead to discontinuation of care were similar to placebo. This approval marks the fourth indication for Caplyta®, the first and only FDA-approved treatment for bipolar I and II depression in adults, as an adjunctive and monotherapy; also approved for the treatment of schizophrenia in adults.

MDD, or clinical depression, is one of the most common psychiatric disorders, affecting about 22 million American adults.4,5 While oral antidepressants may offer relief for some, 2 in 3 people living with MDD continue to experience residual symptoms despite treatment, significantly impacting their overall quality of life.6 Beyond its toll on patients’ wellbeing, MDD has a substantial economic burden and is the leading cause of disability in the U.S.7

“Depression is a complex disorder that affects each person differently, underscoring the urgent need for a range of effective and well-tolerated treatment options,” said Roger S. McIntyre, M.D., FRCPC, Professor of Psychiatry and Pharmacology, University of Toronto.a “For people who are still experiencing lingering depressive symptoms while on an antidepressant, adding Caplyta® to a patient’s treatment regimen may offer early improvement, with the potential for remission—the ultimate goal of treatment.”

This approval is based on positive results from two Phase 3, global, double-blind, placebo-controlled trials – Study 501 and 502 – which both met their primary and key secondary endpoints, providing statistically significant and clinically meaningful improvement in depression symptoms compared to an oral antidepressant plus placebo, as measured by Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression Scale-Severity index (CGI-S) total scores.1,2

A large separation in total MADRS score was seen between Caplyta® and placebo in Study 501 (-4.9 points, effect size 0.61) and Study 502 (-4.5 points, effect size 0.56), at six weeks. Separation from placebo was seen as early as one week in Study 501 and two weeks in Study 502. Significant reductions in the key secondary endpoint of mean change in total CGI-S scores from baseline were also demonstrated at six weeks in Study 501 (-0.7 points, effect size 0.67) and Study 502 (-0.5 points, effect size 0.51).1,2

In pivotal trials, the Caplyta® safety profile was consistent with the existing body of clinical data in its schizophrenia and bipolar depression I and II indications. No new safety concerns were identified. Weight gain and metabolic changes (lipid and glucose levels), as well as akathisia and restlessness, were similar to placebo. Reports of sexual side effects were not common. The most common side effects of Caplyta® include sleepiness, dizziness, nausea, dry mouth, feeling tired, and diarrhea.

“Major depressive disorder affects millions of Americans, impacting how a person feels, thinks, and acts,” said Michael Pollock, CEO of Depression and Bipolar Support Alliance (DBSA). “DBSA believes that all individuals have the right to direct their own treatment, and we understand that for many people, ongoing antidepressant therapy alone may not offer meaningful relief. The introduction of new treatment options, and continued innovation in mental health, has enabled us to reset expectations for living with depression and offers people hope that achieving lasting wellness and remission is possible.”

Long-term data, evidenced by the 503 open-label extension safety study, showed Caplyta® was safe and well tolerated, consistent with the safety profile of Studies 501 and 502. Patients experienced low risk of weight gain, cardiometabolic effects, and extrapyramidal symptoms.8 Caplyta® also demonstrated the potential to help patients achieve remission. During this 26-week safety study, 80% of patients responded to treatment and 65% of patients experienced remission (defined as MADRS Total score ≤ 10) at 6 months.3

Although its exact mechanism of action is unknown, Caplyta® is characterized by high serotonin 5-HT2A receptor occupancy and moderate amounts of dopamine D2 receptor occupancy at therapeutic doses. Caplyta® does not need dose titration, allowing patients to start treatment at the effective dose of 42 mg.8

“Caplyta® has the potential to become a new standard of care across multiple mental health disorders, including major depressive disorder,” said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine. “This approval is a testament to our nearly 70-year commitment of bringing innovative and differentiated therapies that redefine treatment expectations—and introduce the possibility of remission—to patients living with some of today’s most prevalent and debilitating mental health conditions.”

This additional FDA approval builds upon the established, robust clinical efficacy and proven real-world safety profile of Caplyta® for the treatment of adults living with schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder.

A supplemental New Drug Application (sNDA) for Caplyta® with long-term data evaluating the safety and efficacy of the medication for the prevention of relapse in schizophrenia was recently submitted to the FDA. The medication is also being studied for other neuropsychiatric and neurological disorders. Caplyta® is not FDA-approved for these disorders.

https://en.wikipedia.org/wiki/Lumateperone

FDA Approves Caplyta (lumateperone) as an Adjunctive Therapy for the Treatment of Major Depressive Disorder (MDD) in Adults

FDA Approves Zoryve for Atopic Dermatitis in Young Children

In continuation of my update on Zoryve

The U.S. Food and Drug Administration has approved the supplemental new drug application for Zoryve (roflumilast) cream 0.05 percent for the topical treatment of mild-to-moderate atopic dermatitis in children 2 to 5 years of age.

The once-daily cream can be used anywhere on the body and for any duration. This approval offers an alternative to steroids.

The approval is based on clinical trials that showed Zoryve cream rapidly improved the severity and extent of eczema signs and symptoms, with approximately 40 percent of children achieving a 75 percent improvement from baseline on the Eczema Area and Severity Index. Additionally, more than one-third of participants (35 percent) achieved clinically meaningful improvement in itch intensity in four weeks.

"Young children are particularly vulnerable to the bothersome symptoms of atopic dermatitis, because their immune system and skin barrier are less developed than those of older children and adults," Korey Capozza, founder and executive director at Global Parents of Eczema Research, said in a statement. "This condition doesn't just affect the child's skin -- it can affect the whole family by causing sleep disruption, emotional distress, and social isolation."

Approval of Zoryve was granted to Arcutis Biotherapeutics.

More Information

FDA Approves Zoryve for Atopic Dermatitis in Young Children 

Niraparib Plus AAP Improves Survival in mCSPC With HRR Gene Alterations

In continuation of my update on Niraparib

For patients with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR) gene alterations, the addition of niraparib to abiraterone acetate and prednisone (AAP) is beneficial, according to a study published online Oct. 7 in Nature Medicine.

Gerhardt Attard, M.D., Ph.D., from University College London, and colleagues conducted a double-blind trial that evaluated combining niraparib with AAP versus placebo and AAP in mCSPC with HRR gene alterations. A total of 696 patients were randomly assigned to niraparib or placebo (348 each).

Of the patients, 56 percent had BRCA1 or BRCA2 alterations and 78 percent had high-volume metastases. The researchers first observed significant improvement in radiographic progression-free survival in the BRCA subgroup (median not reached at the time of analysis for the niraparib and AAP group versus 26 months for the AAP group; hazard ratio, 0.52). Significant improvement was also seen in the intention-to-treat population (hazard ratio, 0.63). For overall survival, the data were immature but favored niraparib. The incidence of grade 3 or 4 adverse events was 75 and 59 percent in the niraparib and placebo groups, respectively; in the niraparib and AAP group, the most frequent adverse event was anemia (29 percent), with 25 percent of patients needing a blood transfusion.

"For cancers with a mutation in one of the eligible HRR genes, where niraparib has been approved, a doctor should consider a discussion that balances the risks of side effects against the clear benefit to delaying disease growth and worsening symptoms," Attard said in a statement.

Several authors disclosed ties to the biopharmaceutical industry, including Johnson & Johnson, which funded the study.

Abstract/Full Text

https://en.wikipedia.org/wiki/Niraparib

Niraparib Plus AAP Improves Survival in mCSPC With HRR Gene Alterations - Drugs.com MedNews

Tramadol May Have Slight Effect on Reducing Chronic Pain

In continuation of my update on Tramadol..

Tramadol may slightly reduce chronic pain but seems to increase the risk for serious and nonserious adverse events, according to a review published online Oct. 7 in BMJ Evidence-Based Medicine.

Jehad Ahmad Barakji, M.D., from the Centre for Clinical Intervention Research in Copenhagen, Denmark, and colleagues conducted a systematic review to examine the benefits and harms of tramadol versus placebo in chronic pain. Data were included from 19 randomized placebo-controlled trials, with 6,506 participants.

The researchers observed evidence of a beneficial effect of tramadol on chronic pain (mean difference numerical rating scale [NRS], −0.93 points) in a meta-analysis and trial sequential analysis, with the effect size below the predefined minimal important difference of 1.0 point on the NRS. There was evidence of a harmful effect of tramadol on serious adverse events (odds ratio, 2.13), which was mainly due to a higher proportion of cardiac events and neoplasms. Due to a lack of data, it was not possible to conduct a meta-analysis on quality of life. The risk for several nonserious adverse events, including nausea, dizziness, constipation, and somnolence, was increased with tramadol (number needed to harm: seven, eight, nine, and 13, respectively).

"In the United States, the number of opioid-related overdose deaths increased from 49,860 in 2019 to 81,806 in 2022," the authors write. "Given these trends and the present findings, the use of tramadol and other opioids should be minimized to the greatest extent possible."

Abstract/Full Text

Tramadol May Have Slight Effect on Reducing Chronic Pain - Drugs.com MedNews

High Flavanol Consumption May Counteract Sitting-Induced Endothelial Dysfunction

In continuation of my update on Flavanol

Consuming high-flavanol foods and drinks may reduce some of the impact of prolonged sitting on the vascular system, according to a study published online Oct. 29 in the Journal of Physiology.

Alessio Daniele, from the University of Birmingham in the United Kingdom, and colleagues investigated whether intake of dietary flavanols prior to a two-hour sitting bout can preserve upper- and lower-limb endothelial function in high- and low-fit individuals. The analysis included 40 young, healthy men (20 high-fit; 20 low-fit) who completed a two-hour sitting trial after consuming either a high-flavanol (150 mg epicatechin) or low-flavanol (<6 mg epicatechin) cocoa intervention.

The researchers found that sitting significantly reduced flow-mediated dilation (FMD) in the superficial femoral artery and brachial artery. Sitting also increased diastolic blood pressure (BP) in both fitness groups. High-flavanol consumption prevented FMD declines in both arteries, with no effects on BP. There were significant decreases in shear rate and blood flow in both arteries in both fitness groups with sitting, with no effects of the flavanol intervention. Sitting was also associated with declines in tissue oxygenation (TOI), detectable within 10 minutes, and impaired TOI desaturation and speed of reperfusion during hyperemia two hours after sitting, with no effects of flavanols.

"Given how common sedentary lifestyles have become and the increased risk this can have to vascular health, using flavanol-rich food and drink, especially in combination with breaking up periods of inactivity by going for a short walk or standing up, could be a good way to enhance long-term health, no matter the individual's fitness level," coauthor Catarina Rendeiro, also from University of Birmingham, said in a statement.

Abstract/Full Text

https://en.wikipedia.org/wiki/Flavonols

High Flavanol Consumption May Counteract Sitting-Induced Endothelial Dysfunction - Drugs.com MedNews

Intranasal Insulin, Empagliflozin Have Promising Effects on Cognition

In continuation of my update Empagliflozan

Intranasal insulin (INI) and empagliflozin are safe and have promising effects on cognition, according to a study published online Oct. 7 in Alzheimer's & Dementia.

Jennifer M. Erichsen, from the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues conducted a phase 2, 2x2 factorial double-blinded randomized trial involving 47 participants with mild cognitive impairment or early Alzheimer disease or who were amyloid-positive. Participants received INI, the sodium-glucose cotransporter-2 inhibitor empagliflozin, both, or placebo for four weeks. Treatment-related adverse events were examined as the primary outcome.

The researchers found that for all groups, treatment-related adverse events were mild and similar. They also found an increase in modified Preclinical Alzheimer's Cognitive Composite-5, modulated fractional anisotropy and cerebral blood flow, and reduced plasma glial fibrillary acidic protein with INI. Lower cerebrospinal fluid tau and modulated cerebral blood flow were seen with empagliflozin. Immune/inflammatory/neurovascular markers were moderated by both agents.

"For the first time, we found that empagliflozin, an established diabetes and heart medication, reduced markers of brain injury while restoring blood flow in critical brain regions. We also confirmed that delivering insulin directly to the brain with a newly validated device enhances cognition, neurovascular health and immune function. Together, these findings highlight metabolism as a powerful new frontier in Alzheimer's treatment," coauthor Suzanne Craft, Ph.D., also from the Wake Forest University School of Medicine, said in a statement.

Aptar Pharma provided the intranasal delivery devices.

Abstract/Full Text (subscription or payment may be required)

Intranasal Insulin, Empagliflozin Have Promising Effects on Cognition 

AHA: Low-Dose Aspirin Use Linked to Lower ASCVD Outcomes in Type 2 Diabetes

In continuation of my update on aspirin

For adults with type 2 diabetes, low-dose aspirin (ASA) use is associated with a lower risk for myocardial infarction (MI) and stroke, with greater benefit seen with high-frequency use, according to a study presented at the American Heart Association Scientific Sessions 2025, held from Nov. 7 to 10 in New Orleans.

Aleesha Kainat, M.D., from the University of Pittsburgh Medical Center, and colleagues examined the impact of ASA use and adherence frequency on atherosclerotic cardiovascular disease (ASCVD) outcomes among adult patients with diabetes with a moderate or high 10-year ASCVD risk score. Baseline characteristics were balanced between ASA users and nonusers in a propensity score-matched analysis.

Among 11,618 patients, 88.6 and 53.15 percent were ASA and statin users, respectively, at any point during 10-year follow-up. The researchers found that the cumulative incidence of MI, stroke, and 10-year all-cause mortality was significantly lower in the ASA group versus the no-ASA group (42.4 versus 61.2 percent, 14.5 versus 24.8 percent, and 33 versus 50.7 percent, respectively). Compared with no ASA use, any ASA use was associated with significantly lower hazards of MI and ischemic stroke, with greater benefit seen in the high-frequency use group (hazard ratios, 0.54 and 0.47, respectively). Consistent benefit was seen for ASA across glycemic strata, although the magnitude of benefit decreased with worse glycemic control. In better controlled groups, the reduction in mortality was also more pronounced.

"We were somewhat surprised by the magnitude of the findings," Kainat said in a statement. "People with type 2 diabetes and a higher risk of CVD who reported taking low-dose aspirin were much less likely to have had a heart attack, stroke, or death over 10 years when compared to similar individuals who did not report taking low-dose aspirin. That benefit was greatest for those who took aspirin consistently, throughout most of the follow-up time

https://en.wikipedia.org/wiki/Aspirin

AHA: Low-Dose Aspirin Use Linked to Lower ASCVD Outcomes in Type 2 Diabetes - Drugs.com MedNews

Pazopanib Well-Tolerated in Young With Primary Multimetastatic Ewing Sarcoma

In continuation of my update on Pazopanib

For young patients with primary multimetastatic Ewing sarcoma, pazopanib is well-tolerated and effective, according to a study published online Oct. 22 in Frontiers in Oncology.

Noting that pazopanib has been proposed as an effective salvage regimen for soft tissue sarcoma, including extraosseous Ewing sarcoma, Anna Raciborska, M.D., Ph.D., from the Institute of Mother and Child in Warsaw, Poland, and colleagues examined this approach for young patients with primary multimetastatic bone Ewing sarcoma. Eleven patients received standard first-line treatment in parallel with pazopanib.

The researchers found that pazopanib was administered for an average of 1.7 years, throughout the treatment period and after its completion (paused during the surgical procedure). Patients' median age was 14.2 years at the beginning of pazopanib treatment. Five patients underwent surgery on the primary tumor; 10 received concurrent radiation therapy and three underwent autologous hematopoietic stem cell transplantation. No significant toxicities were observed. One, two, and one patients progressed, had relapse, and died (9.1, 18.2, and 9.1 percent, respectively). With a median follow-up of 2.6 years, 10 patients (90.9 percent) were alive. For the whole group, estimated two-year event-free and overall survival were 68.2 and 85.7 percent, respectively.

"Survival rates were higher than in historical controls, suggesting it may extend lives and, importantly, do so without adding severe toxicity," Raciborska said in a statement. "Moreover, the quality of life of treated children was good."

More : Abstract/Full Text

https://en.wikipedia.org/wiki/Pazopanib

Existing drug, Ulipristal acetate- could reduce breast cancer risk in pre-menopausal women

In continuation of my update on Ulipristat

NYU Langone Health researchers found that a type of cell death caused by a buildup of highly reactive molecules suppresses lung tumor growth.

The process, called ferroptosis, evolved to let the body signal for self-destruction of cells that are overly stressed for various reasons. This includes cancer cells, but they in turn evolved to have mechanisms that counter ferroptosis so they can continue their uncontrolled growth despite the stress it creates.

Published in Nature, the new study showed that an experimental treatment blocked the action in cancer cells of a protein called ferroptosis suppressor protein 1 (FSP1) to reduce by up to 80% tumor growth in mice with lung adenocarcinoma (LUAD).

Lung cancer is the leading cause of cancer death worldwide, with LUAD the most common lung cancer among nonsmokers, making up about 40% of cases.

"This first test of a drug that blocks ferroptosis suppression highlights the importance of the process to cancer cell survival and paves the way for a new treatment strategy," said senior study author Thales Papagiannakopoulos, Ph.D., an associate professor in the Department of Pathology at the NYU Grossman School of Medicine.

Harmful reactions

Ferroptosis kills cells by building up levels of iron, which generates highly reactive molecules formed from oxygen, water, and hydrogen peroxide called reactive oxygen species (ROS).

Important for normal cell signaling, ROS also often cause oxidative stress, a disease mechanism in which ROS oxidize (add oxygen molecules to) delicate proteins and DNA to pull them apart. ROS damage fats making up the outer layers of cells to cause cell death and tissue damage.

For the new study, the research team genetically engineered mice to delete the FSP1 gene in lung cancer cells, which led to increased cancer cell death and significantly smaller tumors.

The team also found that a potent, relatively new drug type, an FSP1 inhibitor called icFSP1, improved overall survival of lung tumor-bearing mice, nearly to the extent seen in mice with lung tumors genetically engineered to lack the FSP1 gene.

Their work also showed that Fsp1 is likely a better target for future drugs than another ferroptosis suppressor, glutathione peroxidase 4 (GPX4), which has been studied longer.

FSP1 was shown in the new study to play a greater role in blocking ferroptosis in lung cancer cells specifically, and a smaller role than GPX4 in normal cell functions (likely fewer side effects). Unlike with GPX4, increased FSP1 levels were also found to track with poorer survival in human LUAD patients.

"Our future research will focus on optimizing FSP1 inhibitors and investigating the potential of harnessing ferroptosis as a treatment strategy for other solid tumors, such as pancreatic cancer," said lead study author Katherine Wu, an MD/Ph.D. student working in the Papagiannakopoulos lab.

"We aim to translate these findings from the lab into novel clinical therapies for cancer patients."

https://en.wikipedia.org/wiki/Ulipristal_acetate

Existing drug could reduce breast cancer risk in pre-menopausal women

FDA Issues Complete Response Letter for Biohaven's Vyglxia (troriluzole) New Drug Application for Spinocerebellar Ataxia

Biohaven Ltd. (NYSE: BHVN) ("Biohaven"), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases,  announced  it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of Vyglxia (troriluzole) for the treatment of spinocerebellar ataxia (SCA).

 

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven said, "We are extremely disappointed on behalf of patients by this action from the Office of Neuroscience at FDA. Beyond substantial evidence of safety and efficacy, patients with rare diseases also deserve an efficient, fair and flexible regulatory process that aligns with the urgency of their high unmet medical needs. Such an approach has been mandated by Congress to empower the FDA with maximum regulatory flexibility for rare disease. As a company, we are committed to advancing innovative treatments and remain dedicated to SCA patients despite all the challenges associated with pursuing therapies for rare diseases. Real-world evidence is an important research approach to assessing and delivering new therapies for complex rare diseases but, despite FDA policy initiatives supporting such tools, the front-line review divisions are not yet embracing FDA policy for the use of real-world evidence or the application of regulatory flexibility for rare disease."

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Unit at Massachusetts General Hospital (MGH), added, "Patients with SCA and clinicians who treat them deserve to be heard on this important NDA filing. There is too much at stake for patients. The FDA decision not to listen to disease experts and respect the patient perspective before taking action represents a misstep in the due process, and a failure to deploy regulatory flexibility to evaluate benefit:risk of a medication that has proven to be safe and effective for this rare, debilitating neurodegenerative disease that has no current treatment."

Dr. Coric added, "The development of Vyglxia® (troriluzole) by Biohaven embodies a strong scientific process and deep commitment that is critical to bringing safe and effective treatments to patients with rare diseases like SCA. Our efforts over eight years, included developing the f-SARA scale in collaboration with the FDA and a real-world evidence study in SCA that showed Vyglxia achieved highly consistent, sustained, robust and clinically meaningful treatment effects with a safe, once-daily oral pill that slowed disease progression by 50-70%. The NDA also included data showing Vyglxia reduced the risk of falls and delayed time to becoming wheelchair bound. The leading SCA experts in the United States directly communicated their support of the troriluzole data to the FDA but unfortunately the Office of Neuroscience's inability to collaboratively engage with Biohaven, the patient community and leading experts leave us with concerns about the lack of regulatory flexibility that is being applied for rare, life-threatening conditions. There are a number of common sense solutions and regulatory tools that the Office of Neuroscience could have applied including a fair hearing of the drug's efficacy and safety risks at an Advisory Committee of experts and patients, post-marketing studies, labelling limitations or an accelerated approval pathway. Patients are waiting and the certainty of disease progression for SCA patients far outweighs any residual uncertainty regarding potential design bias or interpretation of study data, especially when the primary outcome measure was achieved in a study protocol and statistical analysis plan that was reviewed by the FDA prior to data analysis. SCA patients deserved approval of Vyglxia and certainly a more balanced interpretation of benefit:risks."

Biohaven remains committed to working with the FDA to find a path forward for its NDA for Vyglxia and plans to meet with the FDA to discuss potential next steps.

Prioritizing Clinical-Stage, Innovative Assets

Biohaven will prioritize resources to focus all its R&D resources on other key programs from its diversified portfolio. Consistent with Biohaven's enduring commitment as a patient-first drug developer, the company's pipeline is focused on a range of disease indications which have limited or no treatment options and are long overdue for therapeutic innovation.

Bruce Car Ph.D., Chief Scientific Officer at Biohaven, commented, "As drug developers we expect setbacks and our diversified portfolio affords us the opportunity to pivot to other key programs. We remain as resilient as ever in following science in order to make a difference in the lives of people with debilitating diseases. Much important work remains, and we are energized and focused on achieving the critical milestones that lie ahead, mindful that days matter and patients are waiting."

Biohaven is initiating strategic portfolio and cost optimization across multiple programs and will focus forward-looking spend on restructuring of business priorities to achieve an approximately 60% reduction in annual direct R&D spend (which excludes personnel and SBC). This may include pausing or delaying non-priority programs to maintain its cash runway to focus on the priority clinical-stage programs over the next year.

https://en.wikipedia.org/wiki/Troriluzole

https://www.drugs.com/nda/vyglxia_251105.html